It has been found that in active RA, high concentrations of M1 macrophages are present in the synovium, and activated macrophages can exacerbate RA by producing pro-inflammatory cytokines and chemokines, such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) [26], which lead to the destruction of articular cartilage and subchondral bone [27]. This evidence concerns the gene IFNG and rheumatoid arthritis.